Type 2 diabetes is a major public health problem with 300 million people predicted to be affected worldwide by 2025. It is a major economic burden. Age-adjusted mortality rates are more than twice as high in subjects with type 2 diabetes, largely due to atherosclerotic vascular disease. The prevalence of type 2 diabetes amongst Australian residents is 7.5%, however prevalence rates up to six times higher have been reported for indigenous Australian communities. The overall aim of the research program is to identify susceptibility genes for type 2 diabetes in the high-risk indigenous Australian population. [unreadable] [unreadable] Two regions of significant linkage have been identified in an indigenous Australian pedigree on chr2q and chr3q. Replication of this linkage in a further fifteen indigenous Australian pedigrees will be established. These regions will be further investigated by fine microsatellite and SNP mapping to define a minimum candidate region. SNP analysis and mutational screening will be undertaken in candidate genes from these regions. Significant associations to type 2 diabetes will be further tested in an additional case control designed study. [unreadable] [unreadable] The specific aims of this project are therefore: [unreadable] 1) Fine mapping and candidate gene analysis in two regions identified by genome-wide scan in a large indigenous Australian pedigree. [unreadable] 2) Replication of the above data in a further fifteen indigenous Australian pedigrees. [unreadable] 3) Isolation of susceptibility genes for type 2 diabetes in indigenous Australians. [unreadable] [unreadable] It is anticipated that genetic studies in this population will yield unique insights into the pathophysiology of this condition. Results from this program of research will be directly applicable to: (i) a more complete understanding of the causes of diabetes (ii) the development of preclinical screening for at-risk subjects, and (iii) the development of novel preventative and therapeutic interventions for more effective management of type 2 diabetes. [unreadable] [unreadable]